The prostate is a male accessory sex gland found in mammals that functions to produce components of the seminal fluid. Development of the prostate begins before birth and continues through sexual maturity. In adulthood the prostate can undergo pathological changes, including benign prostatic hyperplasia and prostate adenocarcinoma. As in many other organs, receptor tyrosine kinase (RTK) signaling plays a major role in regulating prostate development. This proposal is based on preliminary evidence that mutations in the Sprouty genes, which encode key modulators of RTK signaling, as well as in genes that encode components of the RTK signal transduction pathway cause abnormalities in prostate development. The overall goal of this study is to understand the normal function of RTK signaling at early stages of prostate formation and budding, which occur in the embryo, and at later stages of prostate branching and maturation, which occur after birth. This will be accomplished in studies that employ genetic, molecular, and cell biological approaches to determine the consequences of altering RTK signaling in the developing prostate. In the course of these studies we will explore the complex relationship between RTK- and androgen receptor (AR)-mediated signaling in the control of prostate morphogenesis. PUBLIC HEALTH RELEVANCE: The results of these studies will provide insight into the molecular and cell biological mechanisms the regulate prostate development and homeostasis, and thus serve as a foundation for better understanding prostatic disease.